tbuckley/cabot-search huggingface dataset:
Molecular Characterization of Endometrial Carcinomas in Black and White Patients Reveals Disparate Drivers with Therapeutic Implications
Authors: Britta Weigelt, Antonio Marra, Pier Selenica, Eric Rios-Doria, Amir Momeni-Boroujeni, Michael F. Berger, Kanika Arora, David Nemirovsky, Alexia Iasonos, Debyani Chakravarty, Nadeem R. Abu-Rustum, Arnaud Da Cruz Paula, Kimberly Dessources, Lora H. Ellenson, Ying L. Liu, Carol Aghajanian, Carol L. Brown
Journal: Cancer Discovery (2023)

Abstract Although the incidence of endometrial carcinoma (EC) is similar in Black and White women, racial disparities are stark, with the highest mortality rates observed among Black patients. Here, analysis of 1,882 prospectively sequenced ECs using a clinical FDA-authorized tumor–normal panel revealed a significantly higher prevalence of high-risk histologic and molecular EC subtypes in self-identified Black (n = 259) compared with White (n = 1,623) patients. Clinically actionable alterations, including high tumor mutational burden/microsatellite instability, which confer benefit from immunotherapy, were less frequent in ECs from Black than from White patients. Ultramutated POLE molecular subtype ECs associated with favorable outcomes were rare in Black patients. Results were confirmed by genetic ancestry analysis. CCNE1 gene amplification, which is associated with aggressive clinical behavior, was more prevalent in carcinosarcomas occurring in Black than in White patients. ECs from Black and White patients display important differences in their histologic types, molecular subtypes, driver genetic alterations, and therapeutic targets. Significance: Our comprehensive analysis of prospectively clinically sequenced ECs revealed significant differences in their histologic and molecular composition and in the presence of therapeutic targets in Black versus White patients. These findings emphasize the importance of incorporating diverse populations into molecular studies and clinical trials to address EC disparities. This article is featured in Selected Articles from This Issue, p. 2293
Tom Nolan’s research reviews—31 August 2023
Authors: Tom Nolan
Journal: BMJ (2023)

Pred weightHow much should you worry about the effect of weight and blood pressure if prescribing long term low dose glucocorticoids?An analysis of individual data from five randomised controlled trials looked at 1112 people with rheumatoid arthritis who were either taking prednisolone ≤7.5 mg (or equivalent) per day or a control drug.After two years of treatment, those taking prednisolone weighed only 1 kg more than those in the control groups (95% CI 0.4 to 1.8 kg; P<0.001), and there was no difference between groups in mean arterial blood pressure.
Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact — Six U.S. Jurisdictions, November 1–December 14, 2022
Authors: J. Danielle Sharpe, Kelly Charniga, Katrina M. Byrd, Ruth Stefanos, Linda Lewis, Jessica Watson, Amanda Feldpausch, Jessica Pavlick, Julie Hand, Theresa Sokol, Emma Ortega, Preeti Pathela, Robin R. Hennessy, Melissa Dulcey, Lisa McHugh, Michael Pietrowski, Dana Perella, Seema Shah, Azarnoush Maroufi, Melanie Taylor, Anna Cope, Ermias D. Belay, Sascha Ellington, Andrea M. McCollum, Leah Zilversmit Pao, Sarah Anne J. Guagliardo, Patrick Dawson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.
Drug Overdose Deaths with Evidence of Counterfeit Pill Use — United States, July 2019–December 2021
Authors: Julie O’Donnell, Lauren J. Tanz, Kimberly D. Miller, Amanda T. Dinwiddie, Jessica Wolff, Sasha Mital, Rochelle Obiekwe, Christine L. Mattson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Using data from CDC's State Unintentional Drug Overdose Reporting System, this report describes trends in overdose deaths with evidence of counterfeit pill use during July 2019-December 2021 in 29 states and the District of Columbia (DC) and characteristics of deaths with and without evidence of counterfeit pill use during 2021 in 34 states and DC. The quarterly percentage of deaths with evidence of counterfeit pill use more than doubled from 2.0% during July-September 2019 to 4.7% during October-December 2021, and more than tripled in western jurisdictions (from 4.7% to 14.7%). Illicitly manufactured fentanyls were the only drugs involved (i.e., caused death) in 41.4% of deaths with evidence of counterfeit pill use and 19.5% of deaths without evidence. Decedents with evidence of counterfeit pill use, compared with those without evidence, were younger (57.1% versus 28.1% were aged <35 years), more often Hispanic or Latino (18.7% versus 9.4%), and more frequently had a history of prescription drug misuse (27.0% versus 9.4%). Smoking was the most common noningestion drug use route among deaths with evidence of counterfeit pill use (39.5%). Overdose prevention messaging that highlights the dangers of pills obtained illicitly or without a prescription (because they might be counterfeit), encourages drug product testing by persons using drugs, and is tailored to persons most at risk (e.g., younger persons) could help prevent overdose deaths.
A long overdue recognition: COPD as a distinct predictor of cardiovascular disease risk
Authors: Joseph Emil Amegadzie, Mohsen Sadatsafavi
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>There is now robust evidence indicating that COPD is a strong, independent predictor of cardiovascular disease outcomes, so much so that conventional CVD risk-scoring algorithms might generate invalid results in COPD</b>https://bit.ly/3KuRAhi
Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis
Authors: Abir Mukherjee, Divya Bezwada, Francesco Greco, Malu Zandbergen, Tong Shen, Chun-Yi Chiang, Medine Tasdemir, Johannes Fahrmann, Dmitry Grapov, Michael R. La Frano, Hieu S. Vu, Brandon Faubert, John W. Newman, Liam A. McDonnell, Luigi Nezi, Oliver Fiehn, Ralph J. DeBerardinis, Ernst Lengyel
Journal: Nature Metabolism (2023)
Rapid access to antiretroviral therapy, receipt of naltrexone, and strengths-based case management versus standard of care for HIV viral load suppression in people with HIV who inject drugs in Russia (LINC-II): an open-label, randomised controlled trial
Authors: Jeffrey H Samet, Elena Blokhina, Debbie M Cheng, Sydney Rosen, Dmitry Lioznov, Karsten Lunze, Ve Truong, Natalia Gnatienko, Emily Quinn, Natalia Bushara, Anita Raj, Evgeny Krupitsky
Journal: The Lancet HIV (2023)
The sleep, circadian, and cognitive performance consequences of watchkeeping schedules in submariners: A scoping review
Authors: Isabella Marando, Kurt Lushington, Mikaela Owen, Raymond W. Matthews, Siobhan Banks
Journal: Sleep Medicine Reviews (2023)

Watchkeeping schedules are essential for maintaining submarine operations, but come with human risk factors including, disrupted sleep, circadian misalignment, and cognitive deficits. There is now an emerging literature examining the strengths and weaknesses of submarine watchkeeping schedules trialled in the field and under simulated laboratory conditions. The aim of this scoping review was to summarise this literature. A systematic search of peer-reviewed journal articles and industry reports listed in MEDLINE, PsychINFO, PubMed, Scopus, Embase and Google Scholar undertaken in May 2023 returned 7298 papers. Following screening procedures, 13 studies were identified for inclusion. The findings revealed that sleep was sufficiently preserved regardless of watchkeeping schedule (total sleep time = 5.46-7.89 h), circadian misalignment was greater for non-24 h schedules, and longer off-watch periods were associated with better cognitive performance. Taken together, when comparing between watchkeeping schedules, the present findings suggest that the 4 h-on/8 h-off and 8 h-on/16 h-off schedules may be a good compromise when balancing human risk factors and operational demands. However, submarines are complex and challenging environments to study and there is a need to expand the literature. More research comparing watchkeeping schedules is needed. Future studies should focus on cognitive performance measures, such as problem-solving, prioritisation and executive decision-making to address present shortcomings, and an examination of sleep and circadian countermeasures to assist with adaptation either initiated pre-deployment or by modifying the submarine environment itself should be considered.
Rituals and behaviours in the operating theatre and preventing infection. Using the evidence and consensus opinion to provide practical advice
Authors: Hilary Humphreys, Aggie Bak, Elisabeth Ridgway, A. Peter R. Wilson, Margreet C. Vos, Kate Woodhead, Claire Haill, Deborah Xuereb, Joanna M. Walker, Jennifer Bostock, Gemma L. Marsden, Thomas Pinkney, Rashmi Kumar, Peter Hoffman
Journal: Clinical Microbiology and Infection (2023)
Utility of magnetic resonance imaging in the diagnosis of eosinophilic fasciitis: A multicenter retrospective cohort study
Authors: Neda Shahriari, Daniel R. Mazori, Mona Shahriari, Dustin Taylor, Katharina Shaw, Avery H. LaChance, Alisa N. Femia, Ruth Ann Vleugels
Journal: Journal of the American Academy of Dermatology (2023)
Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results
Authors: Adi Diab, Helen Gogas, Shahneen Sandhu, Georgina V. Long, Paolo A. Ascierto, James Larkin, Mario Sznol, Fabio Franke, Tudor E. Ciuleanu, Caio Pereira, Eva Muñoz Couselo, Fernanda Bronzon Damian, Michael Schenker, Aldo Perfetti, Celeste Lebbe, Gaëlle Quéreux, Friedegund Meier, Brendan D. Curti, Carlos Rojas, Yull Arriaga, Haisu Yang, Ming Zhou, Shruthi Ravimohan, Paul Statkevich, Mary A. Tagliaferri, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2023)

PURPOSE Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983 ) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. METHODS Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. RESULTS In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. CONCLUSION The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.
Pan-Cancer Analysis of Postdiagnosis Exercise and Mortality
Authors: Jessica A. Lavery, Paul C. Boutros, Jessica M. Scott, Tuomas Tammela, Chaya S. Moskowitz, Lee W. Jones
Journal: Journal of Clinical Oncology (2023)

The impact of postdiagnosis exercise on cause-specific mortality in cancer survivors and whether this differs on the basis of cancer site is unclear.We performed an analysis of 11,480 patients with cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Patients with a confirmed diagnosis of cancer completing a standardized survey quantifying exercise after diagnosis were included. The primary outcome was all-cause mortality (ACM); secondary end points were cancer mortality and mortality from other causes. Cox models were used to estimate the cause-specific hazard ratios (HRs) for ACM, cancer, and noncancer mortality as a function of meeting exercise guidelines versus not meeting guidelines with adjustment for important clinical covariates.After a median follow-up of 16 years from diagnosis, 4,665 deaths were documented (1,940 due to cancer and 2,725 due to other causes). In multivariable analyses, exercise consistent with guidelines was associated with a 25% reduced risk of ACM compared with nonexercise (HR, 0.75; 95% CI, 0.70 to 0.80). Compared with nonexercise, exercise consistent with guidelines was associated with a significant reduction in cancer mortality (HR, 0.79; 95% CI, 0.72 to 0.88) and mortality from other causes (HR, 0.72; 95% CI, 0.66 to 0.78). The inverse relationship between exercise and cause-specific mortality varied by exercise dose. Exercise consistent with guidelines was associated with a reduced hazard of ACM for multiple cancer sites. Reduction in cancer mortality for exercisers was only observed in head and neck and renal cancer.In this pan-cancer sample of long-term cancer survivors, exercise consistent with guidelines was associated with substantial ACM benefit driven by both reductions in cancer and noncancer mortality. The cause-specific impact of exercise differed as a function of cancer site.
The UK government needs to expand covid-19 vaccination this winter
Authors: Ondine Sherwood, Linda Baines, Amitava Banerjee
Journal: BMJ (2023)

The UK government needs to expand covid-19 vaccination this winterThe covid-19 booster campaign in England will start earlier than planned to counter a new subvariant of covid-19.In this open letter to the secretary of state for health and social care, Long Covid SOS argue that the vaccination rollout will still leave a large proportion of the population unprotected against covid-19 and vulnerable to long term health impacts
Long-Term Outcomes in Patients With Localized Ewing Sarcoma Treated With Interval-Compressed Chemotherapy on Children's Oncology Group Study AEWS0031
Authors: Thomas Cash, Mark D. Krailo, Allen B. Buxton, Bruce R. Pawel, John H. Healey, Odion Binitie, Karen J. Marcus, Holcombe E. Grier, Patrick J. Grohar, Damon R. Reed, Aaron R. Weiss, Richard Gorlick, Katherine A. Janeway, Steven G. DuBois, Richard B. Womer
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Long-term outcomes from Children's Oncology Group study AEWS0031 were assessed to determine whether the survival advantage of interval-compressed chemotherapy (ICC) was maintained over 10 years in patients with localized Ewing sarcoma (ES). AEWS0031 enrolled 568 eligible patients. Patients were randomly assigned to receive vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide alternating once every 3 weeks (standard timing chemotherapy [STC]) versus once every 2 weeks (ICC). For this updated report, one patient was excluded because of uncertainty of original diagnosis. The 10-year event-free survival (EFS) was 70% with ICC compared with 61% with STC ( P = .03), and 10-year overall survival (OS) was 76% with ICC compared with 69% with STC ( P = .04). There was no difference in the 10-year cumulative incidence of second malignant neoplasms (SMNs; P C [see Data Supplement, online only] = .5). A test for interaction demonstrated that ICC provided greater risk reduction for patients with tumor volume ≥200 mL than for patients with tumors &lt;200 mL, but no evidence for a significant interaction in other subgroups defined by age, primary site, and histologic response. With longer-term follow-up, ICC for localized ES is associated with superior EFS and OS without an increased risk for SMN compared with STC. ICC is associated with improved outcomes even in adverse-risk patient groups.
The complex relationship between iron status and anemia in pregnant and postpartum women in India: Analysis of two Indian study cohorts of uncomplicated pregnancies
Authors: Manisha Nair, Saswati S. Choudhury, Anjali Rani, Carolin Solomi, Swapna D. Kakoty, Robin Medhi, Sereesha Rao, Pranabika Mahanta, Farzana Zahir, Indrani Roy, Shakuntala Chhabra, Gitanjali Deka, Bina Minz, Rupanjali Deka, Charles Opondo, David Churchill, Samira Lakhal‐Littleton, Elizabeta Nemeth
Journal: American Journal of Hematology (2023)

Abstract Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low‐and‐middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12–72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] −0.0004, 95% confidence interval [CI] −0.001, 0.001; postnatal: aCoef −0.0001, 95% CI −0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef −0.04, 95% CI −0.07, −0.01), TSAT (aCoef −0.005, 95% CI −0.008, −0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non‐anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency.
Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study
Authors: Ignace Vergote, Els Van Nieuwenhuysen, Roisin E. O'Cearbhaill, Anneke Westermann, Domenica Lorusso, Sharad Ghamande, Dearbhaile C. Collins, Susana Banerjee, Cara A. Mathews, Christine Gennigens, David Cibula, Krishnansu S. Tewari, Kristine Madsen, Fatih Köse, Amanda L. Jackson, Ingrid A. Boere, Giovanni Scambia, Leslie M. Randall, Azmat Sadozye, Jean-François Baurain, Eelke Gort, Michal Zikán, Hannelore G. Denys, Nelleke Ottevanger, Frédéric Forget, Camilla Mondrup Andreassen, Lamar Eaton, Michael J. Chisamore, Leonardo Viana Nicacio, Ibrahima Soumaoro, Bradley J. Monk
Journal: Journal of Clinical Oncology (2023)

PURPOSE Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081 ) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E). CONCLUSION TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.